Dabigatran is the generic name of compound N-[([(amidinophenyl)-amino]methyl)-1-methyl-1H-benzimidazole-5-carbonyl]-N-(2-pyridyl)-3-aminopropionic acid, the chemical structure of which is the following:

Dabigatran is a thrombin specific inhibitor that is given orally in the form of the prodrug dabigatran etexilate. The latter is rapidly absorbed after oral administration and converts to dabigatran, the pharmacologically active molecule, through hydrolysis catalyzed by plasma and liver esterases. The chemical name for dabigatran etexilate is ethyl N—[([([(N′-hexyloxycarbonyl)-amidino]phenyl)amino]methyl)-1-methyl-1H-benzimidazole-5-carbonyl]-N-(2-pyridyl)-3-aminopropionate, and its chemical structure is the following:

Dabigatran and dabigatran etexilate base were first described in patent application WO 98/37075. The mesylate salt of dabigatran etexilate was described in WO 03/74056. In particular example 3 of this document discloses the preparation of dabigatran etexilate mesylate. The resulting product is obtained in a crystalline form characterized by a melting point of 178-179° C. Reproduction of this example by the inventors of the present invention results in a product which corresponds to the crystalline Form I disclosed in WO 2005/028468.
Document WO 2005/028468 discloses two different anhydrous crystalline forms and a hydrated form of dabigatran etexilate mesylate. The crystalline anhydrous forms include Form I, having a melting point of 180±3° C.; and Form II, having a melting point of 190±3° C. The hydrated form has a melting point of 120±5° C.
Document WO 2011/110876 describes in example 15 the preparation of dabigatran etexilate mesylate Form IV characterized by a specific powder X-ray diffraction pattern and by having a melting point of 167-169° C. Reproduction of this example by the inventors of the present invention results in a product which corresponds to the crystalline Form I disclosed in WO 2005/028468.
Document WO 2011/110478 discloses two different non-crystalline forms of dabigatran etexilate mesylate: a solid solution comprising a solid solvent and dabigatran etexilate mesylate dissolved therein; and an amorphous form of dabigatran etexilate mesylate as a composition with one or more hydrophilic polymers, wherein the hydrophilic polymer stabilizes the amorphous state of the active ingredient particles.
The different solid forms of a pharmaceutically active ingredient can have different characteristics, and offer certain advantages, for example with regard to stability, solubility or bioavailability. Thus, the discovery of new solid forms allows for improving the characteristics of the pharmaceutical formulations of the active ingredients, since some forms are more adequate for one type of formulation, and other forms for other different formulations. Furthermore, depending on the therapeutic indications, one or another pharmaceutical formulation may be preferred. It is hence of interest to have new solid forms of dabigatran etexilate mesylate.